tbuckley/cabot-search huggingface dataset:
Computerized features of tumor diversity on pre-chemoradiation MRI are associated with pathologic complete response in rectal cancers: A multi-institutional study.
Authors: Sneha Singh, Thomas DeSilvio, Andrei Purysko, Raj M Paspulati, Ken Friedman, David Liska, Sharon Stein, Smitha S. Krishnamurthi, Satish Easwar Viswanath
Journal: Journal of Clinical Oncology (2022)

3608 Background: Neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) reduces the risk of local recurrence and is a standard-of-care treatment for patients with locally advanced rectal cancer. Previous studies have indicated up to 30% of patients who undergo TME demonstrate a pathologic complete response (pCR) to nCRT [2], but current serum markers and clinical evaluation have limited utility in predicting benefit from nCRT. In this study, we evaluated if tumor diversity features on baseline pre-treatment MRI were predictive of pCR in rectal cancers. Methods: Pre-nCRT T2-weighted MRIs from 126 patients who later underwent nCRT and TME (without neoadjuvant chemotherapy) were retrospectively collected from 2 institutions. 69 patients (14 pCR, Institution 1) formed the training cohort D1, while 57 patients (10 pCR, Institution 2) formed the independent holdout validation cohort D2. Response groupings were based on AJCC tumor regression grade (TRG) evaluation where pCR corresponded to no residual tumor cells in excised histopathologic specimens after nCRT (i.e. TRG0) and non/partial response otherwise (TRG1-3). Computerized tumor diversity algorithms extracted measurements of fractal dimensions, surface topology, and persistent homology from annotated tumor regions on MRI to quantify visual patterns, spatial geometry, and prolonged structural similarity. Top tumor diversity features identified via Wilcoxon rank-sum testing were used to train a random forest (RF) machine learning classifier to predict the likelihood of pCR using D1 and then independently evaluated for predicting pCR in D2. Results: Machine learning analysis identified 5 tumor diversity measurements associated with pCR on pre-nCRT MRI. The associated RF classifier for pCR achieved an AUC of 0.98 (95% CI, 0.9808-0.9949) in D1 and an AUC of 0.9117 in hold-out validation on D2. This corresponded to predicting 100% of non/partial response prior to nCRT as well as 80% of pCR patients via tumor diversity features on pre-nCRT MRI. Conclusions: Computerized tumor diversity features on pre-nCRT MRI can predict pathologic complete response to nCRT in rectal cancers. These findings need to be validated in larger multi-institutional cohorts to establish independent predictive utility of MRI-based biomarkers, which could aid in the selection of patients who will see maximal response from neoadjuvant therapy and avoid unnecessary surgery.
Outcomes of Hispanic and non-Hispanic white pediatric and young adult patients with B-cell acute lymphoblastic leukemia after commercial tisagenlecleucel.
Authors: Panayiotis Vandris, Karen Chao, Christina Baggott, Christine L. Phillips, Muna Qayed, Jenna Rossoff, Stephanie J. Si Lim, Lena E. Winestone, Heather E. Stefanski, Julie-An M. Talano, Steven Margossian, Michael R. Verneris, Gary Douglas Myers, Nicole A. Karras, Patrick A. Brown, Prakash Satwani, Crystal Mackall, Kevin J. Curran, Theodore Willis Laetsch, Liora M. Schultz
Journal: Journal of Clinical Oncology (2022)

10016 Background: Population-level data show significantly inferior outcomes for Hispanic children, adolescents, and young adults (CAYA) diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) relative to non-Hispanic whites (NHW). Here, we compare outcomes between Hispanic and NHW CAYA patients with relapsed and/or refractory (RR) B-ALL receiving tisagenlecleucel, a CD19-specific chimeric antigen receptor (CAR) T cell therapy. Methods: We used data from the Pediatric Real World CAR Consortium retrospective cohort of 200 patients who underwent cell shipment for standard-of-care tisagenlecleucel between August 2017 and March 2020 (N=15 US institutions). Race/ethnicity was identified by medical record review. Patients reported as belonging to more than one racial/ethnic group were classified as multiracial and excluded from analysis. Baseline factors, outcomes, and safety post-infusion were characterized for Hispanic vs. NHW infused patients. Outcomes included complete response (CR) rate, overall survival (OS), duration of response (DOR), and duration of B-cell aplasia (DBA). A multivariate Cox model for OS was constructed, including all baseline factors. Results: Among 185 infused patients, 90 (48.6%) were NHW and 70 (37.8%) were Hispanic. Among 15 non-infused patients, 3 (20.0%) were NHW and 5 (33.3%) were Hispanic. Hispanic patients were significantly older at diagnosis (mean: 10.7 vs. 8.3 years, p=0.02) and had significantly shorter time from diagnosis to infusion (mean: 34.4 vs. 46.4 months, p=0.04). Hispanic and NHW patients did not significantly differ across sex, leukemia type, number of prior lines of therapy, receipt of prior CD19-directed therapy, level of disease burden pre-infusion, and number of relapses pre-infusion. Hispanic and NHW patients did not significantly differ across 1-month CR, 6-month OS, 1-year OS, 18-month OS, 6-month DOR, 1-year DOR, 6-month DBA, and 1-year DBA (Table). On multivariate analysis including the above covariates, OS did not significantly differ for Hispanic patients (HR=1.04, p=0.92). Hispanic and NHW patients did not significantly differ across grade ≥ 3 cytokine release syndrome, grade ≥ 3 neurotoxicity, grade 4 neutropenia, tumor lysis syndrome, or number of infections post-infusion. Conclusions: Outcomes were similar between Hispanic and NHW CAYA RR B-ALL patients receiving tisagenlecleucel in the real-world setting. Increasing access to CAR therapy among Hispanic CAYA B-ALL patients could help mitigate population-level disparities in outcomes observed after receipt of conventional therapies. [Table: see text]
Post-polypectomy surveillance: walking in the fog
Authors: Joaquín Cubiella
Journal: Endoscopy (2022)

Endoscopic surveillance after premalignant polyp resection is aimed at reducing colorectal cancer (CRC) incidence. Unfortunately, we do not have any well-designed prospective randomized trials evaluating the impact of any of the proposed surveillance strategies on CRC incidence. Available recommendations are based mostly on studies with different designs but with a low level of evidence. In fact, endoscopic surveillance accounts for up to 20 % of the colonoscopies performed, with a limited benefit on CRC reduction when compared with participation in CRC screening programs [1].
Pan-cancer analysis of exogenous (microbial) sequences in tumor transcriptome data from the ORIEN consortium and their association with cancer and tumor microenvironment.
Authors: Daniel Spakowicz, Rebecca Hoyd, Caroline E. Wheeler, Yousef Zakharia, Rebecca D. Dodd, Jennifer Ose, Sheetal Hardikar, Ahmad A. Tarhini, Lary A. Robinson, Eric A. Singer, John D. Carpten, Carlos Hou Fai Chan, Alexandra Ikeguchi, Cornelia M Ulrich, Martin McCarter
Journal: Journal of Clinical Oncology (2022)

3113 Background: The tumor microbiome holds great potential for its ability to characterize various aspects of cancer biology and as a target for rational manipulation. For many cancer types, little is known about the role of microbes and in what contexts they affect clinical outcomes. Non-human (i.e. exogenous) sequences can be observed in low abundance within high throughput sequencing data of tumors. Here, we describe a collaboration among members of The Oncology Research Information Exchange Network (ORIEN) to leverage tumor biopsy RNAseq data collected under a shared protocol and generated at a single site to better understand the tumor microbiome, its association with prognostic features of the tumor microenvironment (TME) such as hypoxia, and how it may be used to improve clinical outcomes. Methods: Tumor RNAseq samples from 10 primary source locations including the tissues colon, lung, pancreas, and skin from ORIEN and similar cancers from The Cancer Genome Atlas (TCGA) were processed through the exoTIC (exogenous sequencing in tumors and immune cells) pipeline to identify and count exogenous sequences, filter contaminants, and normalize across datasets. Gene expression signatures of the TME, such as hypoxia, were calculated using ‘tmesig’. Microbe relative abundances were modeled with primary tumor location and hypoxia score using a gamma-distributed generalized linear regression via the stats package in R. Results: We analyzed RNAseq data of 2892 and 2720 tumors from ORIEN and TCGA, respectively. Patients’ ages were significantly greater in the ORIEN than the TCGA dataset (62 vs 58 yo, t-test p&lt;0.001). The ORIEN data contained more sarcoma samples than TCGA (n = 691 vs 259) with roughly equivalent numbers in other cancer types. Fewer microbes were significantly associated with the hypoxia score than with cancer type (n = 32 vs 210). This trend was observed in both the ORIEN and TCGA datasets. The largest effect sizes were observed between microbes and small cell lung cancer. Conclusions: We found microbial sequences in all ORIEN and TCGA tumor RNAseq samples tested. Cancer type showed more significant associations with microbes than a hypoxia signature. These observations merit further investigation into the interaction between microbes and the TME. [Table: see text]
SURG-02. The site of origin of medulloblastoma: Does the neurosurgical perspective support the current concept from molecular data?
Authors: Olga Ciobanu-Caraus, Anna Cho, Gregor Kasprian, Andreas Peyrl, Christine Haberler, Irene Slavc, Josa M Frischer, Thomas Czech, Karl Rössler, Johannes Gojo, Christian Dorfer
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Medulloblastoma (MB) are the most common malignant brain tumor in childhood. Developmental gene expression data supported by neuroradiological studies suggest that Wingless (WNT)-MB originate from the lower rhombic lip (LRL), Sonic-Hedgehog (SHH)-MB from the cerebellar hemispheres, and Group 3 and Group 4 MB from the cerebellar vermis. However, there is still insufficient evidence from a neurosurgical perspective supporting this proposed concept. METHODS: Clinical and molecular data from patients aged under 18 years at time of diagnosis who were operated on a histologically confirmed MB at the Department of Neurosurgery of the Medical University of Vienna between 1990 and 2020 were retrospectively analyzed. The location of the tumor origin was defined based on operative reports, surgical videos and preoperative imaging data by an experienced neurosurgeon blinded to the subgroup information. RESULTS: Sufficient data were available in 53 patients. In 28.6% (2 / 7) WNT-MB, 66.7% (6 / 9) SHH-MB and 70.3% (26 / 37) Group 3 and Group 4 MB, the intraoperatively defined site of origin corresponded well with the cellular origin suspected from the molecular subgroup. Within the WNT-subgroup, 57.1% (4 / 7) originated from the vermis, 28.6% (2 / 7) from the LRL and 14.3% (1 / 7) from the cerebellar hemisphere. The origin of SHH-MB was predominantly located in cerebellar hemispheres (66.7% (6 / 9)), while 33.3% (3 / 9) originated from the vermis. Of Group 3 and Group 4 MB, 70.3% (26 / 37) had their origin in the vermis and 29.7% (11 / 37) in the LRL.CONCLUSION: Our results indicate that there is a considerable level of inconsistency between the intraoperatively observed site of origin and the expected cellular origin based on the molecular subgroup, especially in WNT-MB. This discrepancy needs to be discussed when it comes to surgical decision-making accounting for risk stratification.
Propensity matched comparison of radical cystectomy with trimodality therapy for muscle invasive bladder cancer (MIBC): A multi-institutional study
Authors: A.R. Zlotta, L.K. Ballas, A. Niemierko, K. Lajkosz, C. Kuk, G. Miranda, M. Drumm, A. Mari, E. Thio, N.E. Fleshner, G.S. Kulkarni, P. Chung, R. Bristow, A. Berlin, S. Sridhar, A.S. Feldman, M. Wszolek, R. Lee, A. Zietman, W. Shipley, P. Saylor, S. Daneshmand, J.A. Efstathiou
Journal: European Urology (2022)
A phase II single-center single-arm study of PD-1 inhibitor in combination with albumin paclitaxel and apatinib as second-line treatment of metastatic gastric cancer (mGC).
Authors: Miaomiao Gou, Niansong Qian, Zhikuan Wang, Huan Yan, Yong Zhang, Haiyan Si, Guanghai Dai
Journal: Journal of Clinical Oncology (2022)

e16024 Background: Immune checkpoint inhibitors have been approved for first- or third-line treatment of metastatic gastric cancer. However, pembrolizumab alone did not improve overall survival compared to second-line chemotherapy in the KEYNOTE-061 study. We aimed to explore the safety and efficacy of a three-drug regimen by carrying out a clinical study of PD-1 inhibitor combined with albumin paclitaxel and apatinib (VEGFR inhibitor) in the second-line treatment for patients with metastatic gastric cancer(mGC). Methods: This study was a single-center, single-arm phase II clinical study. patients harboring microsatellite stable (MSS) who had previously failed in first-line treatment were enrolled. The enrolled patients were given PD-1 inhibitor (PD-1 inhibitor selected according to the patients’ requirements) in combination with albumin paclitaxel (125 mg/m 2 IV, D1, 8 days or 250 mg/m 2 IV, D1, 250 mg and apatinib 250 or 500 mg orally for D1-21 days, every 3 weeks as a cycle). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR), while the secondary endpoints were overall survival (OS) and safety (AEs), disease control rate (DCR). Results: From July 11, 2019 to December 1, 2021, a total of 23 patients were enrolled, of whom 10 had negative PD-L1 expression, 1 had PD-L1 &gt; 70% expression, and 4 had positive PD-L1 expression. Preliminary results showed 8 cases had partial response (PR), 10 cases had stable disease (SD), and 5 cases of progression disease (PD). ORR was 34.8% and DCR was 78.3%. The median PFS was 5.04 m, and the median OS was not reached. The main adverse reactions of grade 1 to 2 were bone marrow suppression (42.8%), hand-foot reaction (21.4%), hypertension (21.4%), gastrointestinal bleeding (13.0%), hypothyroidism (8.7%), and liver function damage (8.7%). No grade 3-4 adverse reactions were reported. Conclusions: PD-1 inhibitor combined with albumin paclitaxel and apatinib in the second-line treatment of metastatic gastric cancer showed certain efficacy and safety. At present, this study is ongoing to further confirm the anti-tumor effect and survival benefit of this regimen. Clinical trial information: NCT04182724.
Safety of minimizing intensity of follow-up on active surveillance for clinical stage I testicular germ cell tumors
Authors: P.J. Gariscak, L. Anson-Cartwright, E.G. Atenafu, D.M. Jiang, P. Chung, P. Bedard, P. Warde, M.O. O'Malley, J. Sweet, R.M. Glicksman, R. Hamilton
Journal: European Urology (2022)
Modeling the contribution of preoperative VI-RADS score to predict final pathologic lymph-node involvement in patients with MIBC undergone radical cystectomy
Authors: F. Del Giudice, M. Pecoraro, M. Del Monte, M. Bicchetti, E. Messina, A. Dehghanpour, B.I. Chung, E. De Berardinis, A. Sciarra, V. Panebianco
Journal: European Urology (2022)
A peptide fused to CLDN18.2 antibody targeting the tumor antigen associated CD8+T cells for the treatment of pancreatic cancers.
Authors: Jiajian Liu, Y. Luan, H. Deng, F. Wang, C. Wang, Z. Zhang
Journal: Journal of Clinical Oncology (2022)

e16240 Background: PD-1/PD-L1-targeted immunotherapies have become critical roles in the treatment for many tumors. However, there is limited progress in gastrointestinal cancers, especially in pancreatic ductal adenocarcinoma (PDAC). PDAC is low immunogenicity. PDAC microenvironment is immunosuppressive. More than 70% PDACs have few or no CD8+ T cells around the tumor cell or in the tumor microenvironment. Therefore, immunotherapy like PD-1/PD-L1 antibody alone is rarely effective for PDACs. Methods: Some cytokine or analogs may activate CD8+ T cells. An analog specifically activating tumor antigen associated (TAA) CD8+ T cells was fused to anti-CLDN18.2 antibody. Results: The specific bi-functional molecule (Bis2) has high affinity to human anti-CLDN18.2 (14pM) and CD8+T cells. Bis2 shows significant in vivo efficacy at 0.1 mpk. The efficacy lasts for more than 24 days, only given two doses at day 1 and day 3, respectively. IHC shows that the tumor infiltrated CD8+T cells significantly increased and IFNγ secretion enhanced as well. The IHC results are consistent with the mechanism that Bis2 induces TAA CD8+ T cell proliferation and prevents CD8+T cells from IFNγ-mediated apoptosis. Moreover, Bis2 also shows 100% tumor inhibition in combination with either chem (L-OHP+5FU) or PD-1 antibody in vivo which is better than chem in combination with PD-1 antibody. Bis2 also shows 60% tumor inhibition at 1mpk in CLDN18.2 negative cell based in vivo model. Bis2 shows ADA in monkeys in two weeks by dosing weekly. The repeated doses toxicity study shows an increase of MONO and %MONO and decrease in RBC, HGB, HCT, and MCHC. The HNSTD was 3mpk. The T1/2 was 40h. Conclusions: The Phase I study in advanced solid tumors is ongoing. The study uses accelerated titration starting from 0.01mpk combined with a BOIN design, maximum patient size of 36. In the expansion part, two cohorts of 10 CLDN18.2+ pancreatic cancer patients are planned for the treatment of Bis2 alone or Bis2 in combination with chemotherapy, respectively.
Maintenance endocrine therapy prolonged progression-free survival of first-line chemotherapy with trastuzumab in advanced HR-positive, HER2-positive breast cancer patients.
Authors: Xia-Bo Shen, Jia-Yi Wu, Ke-Yu Chen, Zi-Ru Fang, Guang-Liang Li, Wei-Bin Zou, Xiaojia Wang, Xi-Ying Shao
Journal: Journal of Clinical Oncology (2022)

e13023 Background: Human epidermal growth factor receptor-2 (HER2) positive breast cancer is a growing concern due to the boom in anti-HER2 therapy. Trastuzumab as the most classic anti-HER2 therapy drug, combined with chemotherapy has become the standard first-line treatment for advanced HER2-positive (HER2+) patients. Although some real-world studies of trastuzumab have been reported, less is known about the role of hormone receptors (HR) in first-line combined therapy. For maintenance therapy after chemotherapy combined with anti-HER2 therapy, the guidance given by clinical trials is the maintenance of targeted therapy. However, for those with HER2+/HR-positive (HR+) breast cancer, whether adding endocrine maintenance therapy can benefit progression-free survival (PFS) in addition to anti-HER2 therapy still needs more research. Thus, the purpose of this study was to retrospectively analyze real-world data, determine the factors that influence the trastuzumab-based therapy in advanced HER2-positive breast cancer patients. Methods: We retrospectively collected the treatment information of advanced breast cancer patients underwent first-line chemotherapy with trastuzumab from 2012 to 2021 in Zhejiang Cancer Hospital. Kaplan–Meier analysis and Cox regression methods were used to calculate and compare the PFS. Results: The study finally enrolled 285 patients meeting the requirement, including 150 HER2+/HR-negative (HR-) and 135 HER2+/HR+ (triple-positive) patients. The median chemotherapy treatment cycles and trastuzumab cycles were 7 (6-8) and 12 (7-17) cycles, respectively. For triple-positive breast cancer, maintenance endocrine therapy was aslo given concurrently with trastusumab in 75 patients after chemotherapy and trastusumab. Overally, the median PFS of first-line treatment was 11.73 (10.16-13.30) months, which was consistent with literature reports. Multivariate analysis revealed that HR positive [hazard ratio, 0.69; 95% confidence interval (CI), 0.52–0.92; P= 0.010], and non-brain metastasis (hazard ratio, 0.54; 95% CI, 0.29–0.99; P= 0.048) were independent prognostic factors. Further Kaplan–Meier analysis demonstrated triple-positive patients with maintenance endocrine therapy significantly had longer PFS than triple-positive patients without maintenance endocrine therapy and HER2+/HR- patients (21.33m vs. 10.13m vs. 9.53m, respectively, P &lt; 0.001). Conclusions: HR-positive was an independent prognostic factor for HER2-positive advanced breast cancer patients receiving first-line chemotherapy with trastuzumab. And endocrine therapy combined trastuzumab as Maintenance after chemotherapy prolonged PFS in HR-positive subgroup patients.
First 100 patients of a randomised controlled trial to assess the benefit to apply MOSES™ technology in holmium laser enucleation of the prostate: Surgical and functional outcomes
Authors: A. Pinero Zomeno, A. Narváez Barros, J. Placer Santos, E. Miret Alomar, J. Morote Robles, E. Trilla Herrera
Journal: European Urology (2022)
MEDB-20. The outcome of medulloblastoma patients in the 2010-2018 period in Children’s Hospital Zagreb
Authors: Filip Jadrijevic-Cvrlje, Nada Rajacic, Hrvoje Jednacak, Tonci Grmoja, Ana Tripalo Batos, Miroslav Gjurasin, Jasminka Stepan Giljevic
Journal: Neuro-Oncology (2022)

Abstract This study aims to present the key characteristics of the medulloblastoma patients treated in Children’s Hospital Zagreb and the University Hospital Center Zagreb in Croatia between 2010-2018 period. Croatia has around 145 newly diagnosed pediatric oncology patients annually, including approximately 30 neurooncology patients. We have conducted the retrospective analysis of the hospital records and have collected data on 32 medulloblastoma patients (9 females, 23 males). At the time of diagnosis, the median age was 5,62 (range 0.85-15.86). Before the treatment commencement, we determined conventional risk factors and stratified our patients into standard and high-risk groups (17 standard risk patients, 15 high risk). Qualification for high-risk included metastatic disease, postoperative local residual disease greater than 1.5 cm2, confirmed myc/nmyc amplification in the tumor tissue, and the large cell/anaplastic tumor subtype (p53 positive). The methods of molecular diagnostics were not available at the time. The patients that received solely postoperative chemotherapy were younger than three years. Children younger than five suffering from desmoplastic tumor subtype also received intraventricular methotrexate (Ommaya). High-dosage chemotherapy with autologous stem cell transplantation failed to treat metastatic infant medulloblastoma (2 patients with a lethal outcome). The rest of the patients received craniospinal irradiation, followed by adjuvant chemotherapy. According to the Kaplan-Meier survival analysis, the 5-year overall survival is 65,6 % (40% in the high-risk group and 88% in the standard-risk group). In addition, 5-year event-free survival is 59,4 % (33% in the high-risk group and 82,4% in the standard-risk group). None of the patients developed a secondary malignant disease during the follow-up. Conventional characteristics that determine standard-risk group affiliation are reliable, leading to a satisfactory treatment outcome. The results of the high-risk group treatment are poor necessitating modification treatment approach within clinical trials.